Chapter 19: Disorders Associated with the Immune System

19.1 Hypersensitivity

• The term hypersensitivity refers to an antigenic response that results in undesirable effects.

  • The study of hypersensitivity reactions is called immunopathology.

• The hygiene hypothesis suggests that limiting childhood exposure to bacteria and parasites may lower immune tolerance and limit the body’s ability to cope with harmless antigens, such as food or pollen

• Type I reactions (anaphylactic reactions) occur 2 to 30 minutes after a sensitized person is re-exposed to an antigen.

  • Anaphylaxis is an inclusive term for the reactions caused when antigens combine with IgE antibodies.

• Mast cells are especially prevalent in the mucosal and connective tissue of the skin and respiratory tract and in surrounding blood vessels.

• Basophils in the bloodstream are recruited to the site of an infection.

• Released histamine increases blood flow and the permeability of blood capillaries, resulting in edema (swelling) and erythema (redness).

  • Prostaglandins affect smooth muscles of the respiratory system and increase mucus secretion

• Systemic anaphylaxis (or anaphylactic shock) results when release of mediators causes peripheral blood vessels throughout the body to dilate, resulting in a drop in blood pressure (shock).

• Localized anaphylaxis is usually immediate, temporary, and less severe than systemic anaphylaxis

• ==Asthma is an allergic reaction that mainly affects the lower respiratory system==

• Antigens that enter the body via the gastrointestinal tract can also sensitize an individual

  • Gastrointestinal upset is a common symptom of food allergies, but it can also result from many other factors. Hives are more characteristic of a true food allergy, and ingestion of the antigen may result in systemic anaphylaxis

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19.2 Autoimmune Diseases

• When the immune system acts in response to self-antigens and causes damage to one’s own organs, the result is an autoimmune disease

  • ==Autoimmune diseases occur when there is a loss of self tolerance==, the immune system’s ability to discriminate self from nonself

• Multiple sclerosis is one of the more common autoimmune diseases, affecting mostly younger adult women in temperate areas.

• The etiology of multiple sclerosis is unknown, but epidemiological evidence indicates that it probably involves some infective agent or agents acquired during early adolescence.

• Graves’ disease is a condition in which the thyroid gland is stimulated to produce increased amounts of thyroid hormones

• Myasthenia gravis is a disease in which muscles become progressively weaker.

• Systemic lupus erythematosus is a systemic autoimmune disease involving immune complex reactions, which mainly affects women.

• Crippling rheumatoid arthritis is a disease in which immune complexes of IgM, IgG, and complement are deposited in the joints.

• Insulin-dependent diabetes mellitus is a common condition caused by immunological destruction of insulin-secreting cells of the pancreas.

• The fairly common skin condition psoriasis is an autoimmune disorder characterized by itchy, red patches of thickened skin.

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19.3 Reactions to Transplantation

• A process called HLA typing is used to identify and compare HLAs.

  • Another important medical application of HLA typing is in ==transplant surgery, in which the donor and the recipient must be matched by tissue typing==

• Transplants recognized as nonself are rejected—attacked by T  cells that directly lyse the grafted cells, by macrophages activated by T cells, and, in certain cases, by antibodies, which activate the complement system and injure blood vessels supplying the transplanted tissue.

• A development that promises to transform transplantation medicine is the use of stem cells that are capable of renewing themselves and can be differentiated into other organ-specific specialized cells.

  • Speaking generally, there are embryonic stem cells (ESCs), which can be harvested from a blastocyst (early stage of embryonic development from days 5 to 8 after fertilization

• After birth, these multipotent stem cells are called adult stem cells. They replenish cells, as needed, for various body organs

• Transplants of bone marrow, known as hematopoietic stem cell transplants, are an example of transplantation of adult stem cells.

  • An extremely promising technique for avoiding this problem is the use of umbilical cord blood instead of bone marrow

• A graft is the transfer of a tissue from one part of the body to another, or from one person to another, without the transfer of the blood supply of the grafted tissue

  • This new skin is an example of an autograft. Identical twins have the same genetic makeup; therefore, skin or organs such as kidneys may be transplanted between them without provoking an immune response

• Medical researchers hope to increase the success of xenotransplantation products, which are tissues or organs that have been transplanted from animals

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19.4 The Immune System of Cancer

• Taking advantage of the immune system to prevent or cure cancer led to immunotherapy.

• A vaccine for strains of the human papilloma virus (HPV) that are linked to cervical, anal, and throat cancer is now part of the recommended childhood immunizations in the United States

• Monoclonal antibodies may also be used to boost immune response by flagging cancer cells as something to attack.

  • Another approach is to combine a monoclonal antibody with a toxic agent, forming an immunotoxin.

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19.5 Immunodeficiencies

• The absence of a sufficient immune response is called an immunodeficiency, which can be either congenital or acquired.

• Genetic immune deficiencies can affect complement, phagocytes, B cells, T cells, or a combination of the various immune system actors.

  • A variety of drugs, cancers, or infectious agents can result in acquired immunodeficiencies (secondary immunodeficiencies).

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19.6 Acquired Immunodeficiency Syndrome (AIDS)

• Studies show that HIV-1 (the primary HIV found worldwide in humans) is genetically related to another Lentivirus, simian immunodeficiency virus (SIV), which is carried by monkeys, mangabeys, and chimpanzees in central Africa.
  • ==HIV is often spread by dendritic cells that reside in mucosal linings,== which pick up the virus and carry it to the lymphoid organs.
• Once inside the host cell, viral RNA is released and transcribed into DNA by the enzyme reverse transcriptase.
  • The virus also evades immune defenses by undergoing rapid antigenic changes recommendations for screening vary based on risk of exposure, from once in a lifetime to every 6 months for people who engage in high-risk behaviors (men who have sex with men, people with multiple sex partners, or those who use intravenous street drugs).
• The standard procedure for detecting HIV antibodies has been blood tests using an ELISA test to detect HIV antibodies.
• A problem with antibody-type testing is the window of time between infection and the appearance of detectable antibodies, or seroconversion.
  • The transmission of HIV requires the transfer of, or direct contact with, infected body fluids.
• Routes of HIV transmission include sexual contact, breast milk, transplacental infection of a fetus, blood-contaminated needles, organ transplants, artificial insemination, and blood transfusion.
• Worldwide, heterosexual intercourse is the most common mode of HIV transmission. High-risk sexual behavior and street drug use contribute to the spread of HIV/AIDS.
• Preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) for HIV are used to prevent infection after a recent exposure. PrEP and PEP use drug combinations that are also used in HIV treatment.
  • After virus fusion with the host cell, reverse transcription from the RNA genome produces a double-stranded cDNA copy of the HIV genome.
• The nucleoside reverse transcriptase inhibitors (NRTIs) are analogs of nucleosides and cause the termination of viral DNA by competitive inhibition
• One particularly successful application of chemotherapy has been reducing transmission of HIV from an infected mother to her newborn.

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